Tucumanin, a β-hydroxy-γ-lactone bistetrahydrofuranic acetogenin from Annona cherimolia, is a potent inhibitor of mitochondrial complex I

A new β-hydroxy-γ-methyl-γ-lactone bistetrahydrofuranic acetogenin, tucumanin, with the infrequent symmetrical threo/trans/threo/trans/ threo relative configuration at the tetrahydrofuran rings was isolated from Annona cherimolia (Annonaceae) seeds. The inhibitory potency on the mitochondrial complex I of acetogenins with this relative configuration (tucumanin and asimicin) was compared with that shown by the corresponding pairs with an asymmetrical threo/trans/threo/trans/erythro relative configuration (laherradurin/rolliniastatin-2, and itrabin/molvizarin). All these compounds act as selective inhibitors of mitochondrial complex 1 in the 0.18 - 1.55 nM range.Fil: Barrachina, Isabel. Universidad de Valencia; EspañaFil: Neske, Adriana. Universidad Nacional de Tucumán; ArgentinaFil: Granell, Susana. Universidad de Valencia; EspañaFil: Bermejo, Almudena. Universidad de Valencia; EspañaFil: Chahboune, Nadia. Universidad de Valencia; EspañaFil: El Aouad, Noureddine. Universidad de Valencia; EspañaFil: Alvarez, Olga. Universidad Nacional de Tucumán; ArgentinaFil: Bardon, Alicia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina. Universidad Nacional de Tucumán; ArgentinaFil: Zafra Polo, M. Carmen. Universidad de Valencia; Españ

The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations

Ethnopharmacological relevance: The prevalence of diabetes is on a steady increase worldwide and it is now identified as one of the main threats to human health in the 21st century. In Nigeria, the use of herbal medicine alone or alongside prescription drugs for its management is quite common. We hereby carry out a review of medicinal plants traditionally used for diabetes management in Nigeria. Based on the available evidence on the species׳ pharmacology and safety, we highlight ways in which their therapeutic potential can be properly harnessed for possible integration into the country׳s healthcare system. Materials and methods: Ethnobotanical information was obtained from a literature search of electronic databases such as Google Scholar, Pubmed and Scopus up to 2013 for publications on medicinal plants used in diabetes management, in which the place of use and/or sample collection was identified as Nigeria. ‘Diabetes’ and ‘Nigeria’ were used as keywords for the primary searches; and then ‘Plant name – accepted or synonyms’, ‘Constituents’, ‘Drug interaction’ and/or ‘Toxicity’ for the secondary searches. Results: The hypoglycemic effect of over a hundred out of the 115 plants reviewed in this paper is backed by preclinical experimental evidence, either in vivo or in vitro. One-third of the plants have been studied for their mechanism of action, while isolation of the bioactive constituent(s) has been accomplished for twenty three plants. Some plants showed specific organ toxicity, mostly nephrotoxic or hepatotoxic, with direct effects on the levels of some liver function enzymes. Twenty eight plants have been identified as in vitro modulators of P-glycoprotein and/or one or more of the cytochrome P450 enzymes, while eleven plants altered the levels of phase 2 metabolic enzymes, chiefly glutathione, with the potential to alter the pharmacokinetics of co-administered drugs. Conclusion: This review, therefore, provides a useful resource to enable a thorough assessment of the profile of plants used in diabetes management so as to ensure a more rational use. By anticipating potential toxicities or possible herb–drug interactions, significant risks which would otherwise represent a burden on the country׳s healthcare system can be avoided

Polycerasoidin and polycerasoidol, two new prenylated benzopyran derivatives from polyalthia cerasoides

Two novel metabolites of mixed biogenesis, polycerasoidin [1] and polycerasoidol [2], have been isolated from the stem bark of Polyalthia cerasoides. Their structures were established on the basis of nmr spectroscopic techniques, including 2D correlated nmr spectroscopy (COSY 45, HMQC, and HMBC)

New antitumoral acetogenin “guanacone type” derivatives: isolation and bioactivity. Molecular dynamics simulation of diacetyl-guanacone

We describe herein the isolation and semisynthesis of four acetogenin derivatives (1–4) as well as their ability to inhibit the mitochondrial respiratory chain and several tumor cell lines. In addition, four nanoseconds (ns) of MD simulation of compound 4, in a fully hydrated POPC bilayer, is reported.Fil: Barrachina, Isabel. Universidad de Valencia; EspañaFil: Royo, Inmaculada. Merck, Sharp & Dohme; EspañaFil: Baldoni, Hector Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; ArgentinaFil: Chahboune, Nadia. Universidad de Valencia; EspañaFil: Suvire, Fernando Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; ArgentinaFil: DePedro, Nuria. Merck, Sharp & Dohme; EspañaFil: Zafra Polo, M. Carmen. Universidad de Valencia; EspañaFil: Bermejo, Almudena. Universidad de Valencia; EspañaFil: El Aouad, Noureddine. Universidad de Valencia; EspañaFil: Cabedo, Nuria. Universidad de Valencia; EspañaFil: Saez, Jairo. Universidad de Antioquia; ColombiaFil: Tormo, José R.. Merck, Sharp & Dohme; EspañaFil: Enriz, Ricardo Daniel. Universidad de Antioquia; Colombia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; ArgentinaFil: Cortes, Diego. Universidad de Valencia; Españ